The present study explored the relations among lexical semantics, reading comprehension and contextual clues. The study was modeled on that of Chen’s study, making use of Lexical Semantic Matrix, LSM, designed by Chen in her study, to guide the learners in detecting and organizing contextual clues to meanings of unknown verbs. The LSM was used in Chen’s study as an instructional framework for guiding learners in inferring meanings of unknown nouns. Since verbs rather than nouns are the focus of the present study, the LSM was modified and expanded. Only the experimental group received the instruction on lexical semantics with the help of LSMs, so the present study aimed to find out whether the implementation of LSMs could enhance the students’ vocabulary inferencing ability, reading comprehension, and use of contextual clues. The subjects were from two language drills classes in Tamkang University. The results showed that the LSM seemed to improve the students’ lexical semantic network. In addition, with regard to overall performance on the part of the experimental group, compared with the control group, the experimental group outperformed the control group in three aspects: the total scores, their vocabulary inferencing scores, and frequency of their use of contextual clues. As for the performance on reading comprehension scores, no significant differences were found, which indicated that the experimental group did not perform better than the control group in this aspect.